Control of Transdermal Permeation of Hydrocortisone Acetate from Hydrophilic and Lipophilic Formulations

The purpose of this research was the preparation of four formulations containing hydrocortisone acetate (HCA) for topical application, including two aqueous systems (hydrophilic microemulsion and aqueous gel) and two systems with dominant hydrophobicity (hydrophobic microemulsion and ointment). The formulations were tested for the release and permeation of HCA across an animal membrane. The release of HCA was found comparable for the four systems. The two microemulsions promote permeation across an ex-vivo membrane, examined by means of a Franz cell. Hydrophobic microemulsion guarantees the highest solubility (2,370 μg/ml) and flux (133 μg/cm2.h) of the drug, since it contains almost 40% Transcutol, a permeation enhancer. Gel and ointment provide lower solubility and flux, being the values, related to the ointment, the lowest ones (562 μg/ml and 0.4 μg/cm2.h). Experimental results allow the conclusion that gel and ointment can be suitable when it is desirable to minimize absorption of topically applied HCA as to keep the drug restricted to the diseased area and prevent side effects of the systemic presence of HCA

Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes

Background Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis). Results We conducted a randomized, double-blinded, placebo-controlled pilot trial (NCT02877277) in Danish patients with myeloid cancers performed during 3 cycles of DNMTi-treatment (5-azacytidine, 100 mg/m2/d for 5 days in 28-day cycles) supplemented by oral dose of 500 mg vitamin C (n = 10) or placebo (n = 10) daily during the last 2 cycles. Fourteen patients (70%) were deficient in plasma vitamin C (< 23 μM) and four of the remaining six patients were taking vitamin supplements at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (< 11.4 μM; 4.997 vs 4.656% 5mC relative to deoxyguanosine, 95% CI [0.126, 0.556], P = 0.004). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (mean increase 34.85 ± 7.94 μM, P = 0.0004). We show for the first time that global 5hmC/5mC levels were significantly increased in mononuclear myeloid cells from patients receiving oral vitamin C compared to placebo (0.037% vs − 0.029%, 95% CI [− 0.129, − 0.003], P = 0.041). Conclusions Normalization of plasma vitamin C by oral supplementation leads to an increase in the 5hmC/5mC ratio compared to placebo-treated patients and may enhance the biological effects of DNMTis. The clinical efficacy of oral vitamin C supplementation to DNMTis should be investigated in a large randomized, placebo-controlled clinical trial

Measurements of D0D^{0} and D∗D^{*} Production in pp + pp Collisions at s\sqrt{s} = 200 GeV

We report measurements of charmed-hadron ($D^{0}$, $D^{*}$) production cross sections at mid-rapidity in $p$ + $p$ collisions at a center-of-mass energy of 200 GeV by the STAR experiment. Charmed hadrons were reconstructed via the hadronic decays $D^{0}\rightarrow K^{-}\pi^{+}$, $D^{*+}\rightarrow D^{0}\pi^{+}\rightarrow K^{-}\pi^{+}\pi^{+}$ and their charge conjugates, covering the $p_T$ range of 0.6$-$2.0 GeV/$c$ and 2.0$-$6.0 GeV/$c$ for $D^{0}$ and $D^{*+}$, respectively. From this analysis, the charm-pair production cross section at mid-rapidity is $d\sigma/dy|_{y=0}^{c\bar{c}}$ = 170 $\pm$ 45 (stat.) $^{+38}_{-59}$ (sys.) $\mu$b. The extracted charm-pair cross section is compared to perturbative QCD calculations. The transverse momentum differential cross section is found to be consistent with the upper bound of a Fixed-Order Next-to-Leading Logarithm calculation.Comment: 15 pages, 16 figures. Revised version submitted to Phys. Rev.

Inclusive charged hadron elliptic flow in Au + Au collisions at sNN\sqrt{s_{NN}} = 7.7 - 39 GeV

A systematic study is presented for centrality, transverse momentum ($p_T$) and pseudorapidity ($\eta$) dependence of the inclusive charged hadron elliptic flow ($v_2$) at midrapidity($|\eta| < 1.0$) in Au+Au collisions at $\sqrt{s_{NN}}$ = 7.7, 11.5, 19.6, 27 and 39 GeV. The results obtained with different methods, including correlations with the event plane reconstructed in a region separated by a large pseudorapidity gap and 4-particle cumulants ($v_2{4}$), are presented in order to investigate non-flow correlations and $v_2$ fluctuations. We observe that the difference between $v_2{2}$ and $v_2{4}$ is smaller at the lower collision energies. Values of $v_2$, scaled by the initial coordinate space eccentricity, $v_{2}/\varepsilon$, as a function of $p_T$ are larger in more central collisions, suggesting stronger collective flow develops in more central collisions, similar to the results at higher collision energies. These results are compared to measurements at higher energies at the Relativistic Heavy Ion Collider ($\sqrt{s_{NN}}$ = 62.4 and 200 GeV) and at the Large Hadron Collider (Pb + Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV). The $v_2(p_T)$ values for fixed $p_T$ rise with increasing collision energy within the $p_T$ range studied ($< 2 {\rm GeV}/c$). A comparison to viscous hydrodynamic simulations is made to potentially help understand the energy dependence of $v_{2}(p_{T})$. We also compare the $v_2$ results to UrQMD and AMPT transport model calculations, and physics implications on the dominance of partonic versus hadronic phases in the system created at Beam Energy Scan (BES) energies are discussed.Comment: 20 pages, 12 figures. Version accepted by PR

Studies of di-jet survival and surface emission bias in Au+Au collisions via angular correlations with respect to back-to-back leading hadrons

We report first results from an analysis based on a new multi-hadron correlation technique, exploring jet-medium interactions and di-jet surface emission bias at RHIC. Pairs of back-to-back high transverse momentum hadrons are used for triggers to study associated hadron distributions. In contrast with two- and three-particle correlations with a single trigger with similar kinematic selections, the associated hadron distribution of both trigger sides reveals no modification in either relative pseudo-rapidity or relative azimuthal angle from d+Au to central Au+Au collisions. We determine associated hadron yields and spectra as well as production rates for such correlated back-to-back triggers to gain additional insights on medium properties.Comment: By the STAR Collaboration. 6 pages, 2 figure